The use of cocaine as an illegal drug is reaching epidemic proportions. Yet, the physiological and biochemical effects of the drug are poorly understood. This is especially true in relation to exercise physiology in spite of the widespread use of this drug among competitive athletes as well as recreational participants. The hazards encountered by users of cocaine prior to exercise have not been described, but it can be speculated that, since cocaine and exercise both act to enhance the sympathetic system, such an additive effect could have serious consequences on all physiological systems under sympathetic control such as muscle blood flow, substrate mobilization and utilization, myocardial metabolism, liver metabolism, as well as endocrine function. There is virtually no information regarding the effects of cocaine on these physiological systems either at rest or during exercise. Thus, the purpose of this project is to use the exercising rat model as a tool for studying 1) the effects of various doses of cocaine on resting physiology (dose-response), 2) the effects of various doses on the physiological response to exercise, 3) the effect of various doses on cardiac metabolism during exercise, 4) the chronic effects of cocaine use (addiction) on the acute response to exercise, and 5) the chronic effects of cocaine use on the normal adaptive response to endurance training. Parameters to be assessed ineach of these studies include 1) liver and muscle glycogen metabolism, 2) blood substrate changes (FFA, glucose, lactic acid), and 3) hormonal changes (catecholamines, glucagon, insulin, glucocorticoid). In addition glucose-6-phosphate and citrate levels will be measured in heart. The effects on certain aerobic and anaerobic enzymes will also be examined in the training studies. It seems logical to evaluate the physiology of cocaine using the exercise model, since exercise creates such marked alteration in a number of physiological systems. Fortunately, these alterations are well characterized, and thus can serve as markers for any effects of cocaine. Furthermore, cocaine has the reputation of being a performance enhancer, yet this belief is based on superficial data, very little of which is physiological. For these purposes the study of cocaine and exercise seems to be extremely important. This project could provide valuable information that could be used as a basis for future studies to investigate the mechanism by which cocaine might exert its effects peripherally. Such would be our long range research goal.